Progression of osseous lesions: progression or appearance of two or more lesions on bone scan or soft tissue lesions using Response Evaluation Criteria in Solid Tumours and with nodes >2 cm in diameter
In view of the apparent lack of superior activity and greater toxicity by the addition of estramustine, docetaxel every 3 weeks plus low-dose prednisone can be considered as the current standard treatment
The optimal duration of docetaxel based chemotherapy for CRPC has not yet been established.
Tax 327 10 cycles
SWOG 99-16 12 cycles.
Standard practice is to treat patients with a ﬁxed number of 10cycles of chemotherapy
PCWG 2 deﬁned criteria of progression on the basis of changes in PSA, bone metastases, and measurable disease
PSA progression has been deﬁned as a 25% or greater increase and an absolute increase of 2ng/mL or more from the lowest documented PSA level,which is conﬁrmed by a second value obtained 3 or more weeks later.
When the bone scan is the sole indicatorof progression- when at least two or more new lesions are seen on a bone scan compared with prior scans.
Measurable ds- RECIST
Surrogate markers- 30% decline in PSA at 3 months and Post treatment PSA velocity
CALGB 90401-Despite improvement in PFS, measurable disease response and post-therapy PSA decline, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC, and was associated with greater morbidity and mortality
Bone metastases from hormone-refractory (castration-resistant) prostate cancer (CRPC) are associated with RANKL-mediated osteoclast activation resulting in bone destruction and skeletal-related events (SRE)
Denosumab is a fully human monoclonal antibody against RANKL
120 mg subcut 4 weekly with ca and vit d supp
Denosumab demonstrated superiority over ZA in delaying or preventing SREs in patients with bone metastases from CRPC.
Adverse events were consistent in both treatment groups with those previously reported in advanced cancer populations.